Figure 7. Model for USP3-dependent deubiquitination of γH2AX in regulation of DDR. In response of DNA damage such as UV- or IR-induced DNA breaks, K13–15 of γH2AX is ubiquitinated by the concerted action of RNF168 and RNF8. The ubiquitinated γH2AX, in turn, facilitates the accumulation of DNA break repair factor BRCA1 and 53BP1, leading to the choice of HR or NHEJ repair pathways. USP3 negatively regulates the accumulation of BRCA1 and 53BP1 at DNA breaks by virtue of deubiquitinating γH2AX.